Condition category
Pregnancy and Childbirth
Date applied
19/11/2018
Date assigned
21/12/2018
Last edited
22/06/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Suspended

Plain English Summary

Current plain English summary as of 17/06/2020:

Background and study aims
Diabetes during pregnancy or gestational diabetes mellitus (GDM) is associated with significant pregnancy-related complications, morbidity in newborns, and a long-term risk of developing type 2 diabetes, obesity and cardiovascular disease in both the mother and the offspring. In pregnant women with GDM, blood sugar usually returns to normal levels after delivery. However, about 50-70% of GDM mothers develop type 2 diabetes within 5-10 years after the birth of the child. Simple lifestyle interventions such as dietary modification and regular physical activity have shown to improve blood sugar levels and constitute potentially attractive options to reduce the risk of GDM. The current study aims to investigate if diet and/or physical activity intervention from earlier than 18 weeks of pregnancy helps reduce the risk of developing diabetes during pregnancy.

Who can participate?
Pregnant women aged 18 years or older and over and pregnancy for 16 weeks or less duration with at least one risk factor for developing diabetes during pregnancy.

What does the study involve?
Eligible women will be randomly allocated to one of the four treatment groups – diet, physical activity, diet and physical activity or standard care. In the dietary intervention, women will have to consume 200 g of fermented yoghurt daily. Women randomized to the physical activity (PA) group will have to undertake daily walking calculated as 40% more than their baseline activity monitored by device and the diet and PA group will have both interventions as above. All interventions will last for a minimum duration 14 weeks from randomization. Women allocated to standard care arm will serve as controls and will not be subjected to any active intervention, but will receive routine care by their treating physician. Participants will be studied for development of diabetes at 26 - 28 weeks and 32 weeks of pregnancy. Women who are diagnosed to have diabetes at 26-28 weeks could voluntarily withdraw from interventions or continue to 32 weeks on active interventions along with appropriate diabetes management as per local clinical practice. At 32 weeks of pregnancy final assessment of diabetes status will be done and all study procedures will be completed. Data of the mother and the newborn's health will be collected at delivery.

What are the possible benefits and risks of participating?
The possible benefit for participants is better pregnancy care and early screening for diabetes. The current study provides women with experience of specific healthy lifestyles during pregnancy. The opportunity to bring about behavioural changes during early pregnancy by changing mother’s nutrition and increasing physical activity to prevent GDM can have immediate and lifelong health impacts on the mother, as well as the newborn, with possible positive consequences into adulthood. There are no known risks to participants taking part in the study. Both yoghurt and physical activity are generally considered safe during pregnancy.

Where is the study run from?
The study is run from the Oxford Centre for Diabetes, Endocrinology and Metabolism (UK) and will take place in a centre in India and a centre in The Gambia

When is the study starting and how long is it expected to run for?
September 2018 to August 2021

Who is funding the study?
1. Medical Research Council (UK)
2. Director of Biotechnology (India)
3. Global Challenges Research Fund (UK)

Who is the main contact?
Dr Senthil Vasan
senthil.vasan@ocdem.ox.ac.uk

_____

Previous plain English summary from 07/05/2020 to 16/06/2020:

Background and study aims
Diabetes during pregnancy or gestational diabetes mellitus (GDM) is associated with significant pregnancy-related complications, morbidity in newborns, and a long-term risk of developing type 2 diabetes, obesity and cardiovascular disease in both the mother and the offspring. In a pregnant women with GDM, blood sugar usually returns to normal levels after delivery. However, about 50-70% of GDM mothers develop type 2 diabetes within 5-10 years after the birth of the child. Simple interventions such as dietary modification and regular physical activity have shown to improve blood sugar levels and constitute potentially attractive options to reduce the risk of GDM.
The current study aims to investigate if diet and physical activity intervention from less than 18 weeks of pregnancy helps reduce the risk of developing diabetes among pregnant women.

Who can participate?
Pregnant adult women who have been pregnant for 16 weeks or less and are at risk of developing diabetes during pregnancy

What does the study involve?
Eligible women will be randomly allocated to one of the four treatment groups – diet, physical activity, diet and physical activity or standard care. In the dietary intervention, women will have to consume 200 g of fermented yoghurt daily. Women randomized to the physical activity group will have to undertake 40% more than their baseline activity monitored by device. All interventions will last for a total duration of 14 weeks (from 18 to 32 weeks of pregnancy). Women allocated to standard care arm will serve as controls and will not be subjected to any active intervention, but will receive routine care by their treating physician. Participants will be studied for development of diabetes at 26 - 28 weeks of pregnancy. Women who are diagnosed to have diabetes at this stage will be terminated from further intervention and diabetes management will be provided as per local clinical practice. Women who do not develop diabetes, will continue intervention till 32 weeks of pregnancy where final assessment of diabetes status will be done and all study procedures will be completed.

What are the possible benefits and risks of participating?
The possible benefit for participants is better pregnancy care and screening for diabetes. The current study provide women with experience of specific healthy lifestyles during pregnancy. The opportunity to bring about behavioural changes during early pregnancy by changing mother’s nutrition and increasing physical activity to prevent GDM can have immediate and lifelong health impacts on the mother, as well as the newborn, with possible positive consequences into adulthood. The effect of diet and lifestyle interventions in reducing diabetes risk is well known and such interventions would largely benefit both the mother and the new born child in long term. There are no known risks to participants taking part in the study. Both yoghurt and physical activity are generally considered safe during pregnancy.

Where is the study run from?
The study is run from the Oxford Centre for Diabetes, Endocrinology and Metabolism (UK) and will take place in a centre in India and a centre in The Gambia

When is the study starting and how long is it expected to run for?
September 2018 to August 2021

Who is funding the study?
1. Medical Research Council (UK)
2. Director of Biotechnology (India)
3. Global Challenges Research Fund (UK)

Who is the main contact?
Dr Senthil Vasan
senthil.vasan@ocdem.ox.ac.uk

_____

Previous plain English summary:

Background and study aims
Diabetes during pregnancy or gestational diabetes mellitus (GDM) is associated with significant pregnancy-related complications, morbidity in newborns, and a long-term risk of developing type 2 diabetes, obesity and cardiovascular disease in both the mother and the offspring. In a pregnant women with GDM, blood sugar usually returns to normal levels after delivery. However, about 50-70% of GDM mothers develop type 2 diabetes within 5-10 years after the birth of the child. Simple interventions such as dietary modification and regular physical activity have shown to improve blood sugar levels and constitute potentially attractive options to reduce the risk of GDM.
The current study aims to investigate if diet and physical activity intervention from 18 weeks of pregnancy helps reduce the risk of developing diabetes among pregnant women.

Who can participate?
Pregnant adult women who have been pregnant for 16 weeks or less and are at risk of developing diabetes during pregnancy

What does the study involve?
Eligible women will be randomly allocated to one of the four treatment groups – diet, physical activity, diet and physical activity or standard care. In the dietary intervention, women will have to consume 200 g of fermented yoghurt daily. Women randomized to the physical activity group will have to undertake daily walking to a target step count of 11,000 steps/day or 40% more than their baseline activity monitored by device. All interventions will last for a total duration of 14 weeks (from 18 to 32 weeks of pregnancy). Women allocated to standard care arm will serve as controls and will not be subjected to any active intervention, but will receive routine care by their treating physician. Participants will be studied for development of diabetes at 24-26 weeks of pregnancy. Women who are diagnosed to have diabetes at this stage will be terminated from further intervention and diabetes management will be provided as per local clinical practice. Women who do not develop diabetes, will continue intervention till 32 weeks of pregnancy where final assessment of diabetes status will be done and all study procedures will be completed.

What are the possible benefits and risks of participating?
The possible benefit for participants is better pregnancy care and screening for diabetes. The current study provide women with experience of specific healthy lifestyles during pregnancy. The opportunity to bring about behavioural changes during early pregnancy by changing mother’s nutrition and increasing physical activity to prevent GDM can have immediate and lifelong health impacts on the mother, as well as the newborn, with possible positive consequences into adulthood. The effect of diet and lifestyle interventions in reducing diabetes risk is well known and such interventions would largely benefit both the mother and the new born child in long term. There are no known risks to participants taking part in the study. Both yoghurt and physical activity are generally considered safe during pregnancy.

Where is the study run from?
The study is run from the Oxford Centre for Diabetes, Endocrinology and Metabolism (UK) and will take place in a centre in India and a centre in The Gambia

When is the study starting and how long is it expected to run for?
September 2018 to August 2021

Who is funding the study?
1. Medical Research Council (UK)
2. Director of Biotechnology (India)
3. Global Challenges Research Fund (UK)

Who is the main contact?
Dr Senthil Vasan
senthil.vasan@ocdem.ox.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Senthil Vasan

ORCID ID

http://orcid.org/0000-0002-3630-6568

Contact details

Oxford Centre for Diabetes
Endocrinology and Metabolism
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
+44 (0)7575323737
senthil.vasan@ocdem.ox.ac.uk

Type

Scientific

Additional contact

Prof Fredrik Karpe

ORCID ID

Contact details

Oxford Centre for Diabetes
Endocrinology and Metabolism
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
+44 1865 857222
fredrik.karpe@ocdem.ox.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MR/R020345/1

Study information

Scientific title

Pregnancy-Related Interventions in Mothers at Risk for gestational Diabetes in Asian India and Low and middle income countries (PRIMORDIAL Study)

Acronym

PRIMORDIAL

Study hypothesis

Daily yoghurt and/or daily walking for at least 14 weeks will reduce the risk of developing gestational diabetes in ‘high-risk’ pregnant women

Ethics approval

1. Oxford Tropical Research Ethics Committee (OxTREC), 01/11/2018, 44-18
2. Christian Medical College, Vellore, 27/06/2018, IRB:11367
3. Scientific Co-ordinating Committee, MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, 13/11/2018, SCC 1645v1.1

Study design

Interventional 2x2 factorial randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Gestational diabetes mellitus

Intervention

Current interventions as of 17/06/2020:

Participants will be randomly allocated to either the intervention or the control group.
Participants in the intervention group will be further randomised to receive either 200 g/day yoghurt, a physical activity intervention or both. This physical activity intervention will involve daily walking to a step count 40% higher than their baseline physical activity recorded during run-in-phase.
Participants in the control group will receive standard care with no specific intervention
Randomisation will be centre specific and stratified based on age and body mass index within each randomisation block.
The total duration of the intervention is 14 weeks. Participants will be randomised within 2 weeks of screening and active intervention will continue till 32 weeks as per protocol. However, if any participant develops diabetes prior to 32 weeks, further continuation in the intervention will depend on safety, the effect of continuing interventions on pregnancy and subject to the investigator. GDM will be managed according to local guidelines in these participants.

_____

Previous interventions from 07/05/2020 to 16/06/2020:

Participants will be randomly allocated to either the intervention or the control group.
Participants in the intervention group will be further randomised to receive either 200 g/day yoghurt, a physical activity intervention or both. This physical activity intervention will involve daily walking to a step count 40% higher than their baseline physical activity.
Participants in the control group will receive standard care with no specific intervention.
Randomisation will be centre specific and stratified based on age and body mass index within each randomisation block.
The total duration of intervention is 14 weeks. Participants will be randomised at ≤ 18 weeks gestation and the intervention will continue till 32 weeks as per protocol. However, if any participant develops diabetes prior to 32 weeks, active trial interventions will be stopped.

_____

Previous interventions:

Participants will be randomly allocated to either the intervention or the control group.
Participants in the intervention group will be further randomised to receive either 200 g/day yoghurt, a physical activity intervention or both. This physical activity intervention will involve daily walking to a step count 40% higher than their baseline physical activity, or walking daily to a step count of 11,000 steps (whichever is the greatest).
Participants in the control group will receive standard care with no specific intervention.
Randomisation will be centre specific and stratified based on age, body mass index and history of gestational diabetes during previous pregnancy within each randomisation block.
The total duration of intervention is 14 weeks. Participants will be randomised at 18 weeks gestation and the intervention will continue till 32 weeks as per protocol. However, if any participant develops diabetes prior to 32 weeks, active trial interventions will be stopped.

Intervention type

Mixed

Phase

Drug names

Primary outcome measure

Current primary outcome measure as of 07/05/2020:

Incidence of gestational diabetes mellitus diagnosed based on IADPSG criteria at 26-28 weeks or fasting plasma glucose ≥5.1 mmol/l at week 32 (plasma glucose analysed using a Roche Cobas 800 Enzymic autoanalyser)

_____

Previous primary outcome measure:

Incidence of gestational diabetes mellitus according to IADPSG criteria, assessed by the following during weeks 26-28 of gestation and at 32 weeks of gestation:
1. Fasting plasma glucose, analysed using a Roche Cobas 800 Enzymic autoanalyser
2. Glucose at 1 and 2 hours post 75 g oral glucose tolerance test (OGTT), analysed using a Roche Cobas 800 Enzymic autoanalyser

Secondary outcome measures

Current secondary outcome measures as of 07/05/2020:

1. Absolute values of fasting blood glucose concentration at 32 weeks gestational age
2. Gestational weight gain using a Digital Tanita scale (in The Gambia) and a stadiometer (in India) from randomisation to week 32
3. Blood pressure from randomisation to week 32
4. Proportion of women undergoing instrumental/caesarean delivery, assessed using the study proforma
5. Post-partum haemorrhage,assessed using the amount of blood loss after child birth from the study proforma at delivery
6. Pre-eclampsia and eclampsia, assessed using clinical diagnosis of hypertension and proteinuria (with or without seizures) from the study proforma after 28 weeks of gestation
7. Blood loss at delivery, assessed using the amount of blood loss during the delivery from the study proforma at delivery
8. Pre-term births (less than 37 weeks of gestation), determined by calculating gestational age from dating the ultrasound scan at delivery
9. Foetal macrosomia (defined as birth weight >2 standard deviations above the population-specific mean in each setting), assessed from birth weight measured using an infantometer at delivery
10. Birth weight, assessed using an infantometer at delivery
11. Physical condition of newborn infant, assessed using the clinically recorded APGAR score at 1 and 5 minutes of birth
12. Length of newborn, assessed by measuring length from the head to the heel using a non-stretchable tape within 48 hours of birth.
13. Barriers to interventions in pregnancy, assessed using a questionnaire at screening and at 32 weeks of gestation

_____

Previous secondary outcome measures:

1. Gestational weight gain, assessed using a Digital Tanita scale (in The Gambia) and a stadiometer (in India) at screening, the run-in phase, the point of randomisation, visits 1, 2 and 3, and at delivery (prior to birth)
2. Requirement of insulin/metformin post-OGTT, assessed through a review of patient notes from the diagnosis of GDM to delivery
3. Proportion of women undergoing instrumental/caesarean delivery, assessed using the study proforma after delivery
4. Gestational age at delivery, determined by dating the ultrasound scan at delivery
5. Post-partum haemorrhage, assessed using the amount of blood loss after child birth from the study proforma at delivery
6. Pre-eclampsia and eclampsia, assessed using clinical diagnosis of hypertension and proteinuria (with or without seizures) from the study proforma after 28 weeks of gestation
7. Blood less at delivery, assessed using the amount of blood loss during the delivery from the study proforma at delivery
8. Pre-term births (less than 37 weeks of gestation), determined by calculating gestational age from dating the ultrasound scan at delivery
9. Foetal macrosomia (defined as birth weight >2 standard deviations above the population-specific mean in each setting), assessed from birth weight measured using an infantometer at delivery
10. Low birth weight (defined as birth weight <2.5 kg), assessed using an infantometer at delivery
11. Physical condition of newborn infant, assessed using the clinically recorded APGAR score at 1 and 5 minutes of birth
12. Length of newborn, assessed by measuring length from the head to the heel using a non-stretchable tape within 48 hours of birth
13. Ponderal index, assessed using the formula (birth weight (kg)/birth length (m))³ within 48 hours of birth
14. Abdominal circumference of the newborn, assessed by measuring the circumference at the level of the xiphisternum and just above/below the level of the umbilicus using non-stretchable tape within 48 hours of birth
15. Barriers to interventions in pregnancy, assessed using a questionnaire at screening and at 32 weeks of gestation

Overall trial start date

01/09/2018

Overall trial end date

21/08/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 07/05/2020:

1. Aged 18 years or older
2. Gestational age ≤ 16 weeks
3. Meeting at least one of the following criteria for high-risk gestational diabetes mellitus (GDM):
3.1. Booking BMI ≥ 25kg/m²
3.2. Age ≥ 25 years
3.3. First-degree relative with diabetes
3.4. Previous pregnancy with GDM
3.5. Previous pregnancy with large baby (≥ 3.5kg)
3.6. Previous pregnancy with pre-eclampsia/eclampsia
3.7. History of PCOD/impaired fasting glucose)
4. Not currently on any medications (except iron, calcium or folic acid supplements, thyroxine supplement for hypothyroidism, low dose aspirin for pre-eclampsia)

_____

Previous inclusion criteria:

1. Aged 18 years or older
2. Pregnant females
3. Gestational age >16 weeks
4. Meeting at least one of the following criteria for high-risk gestational diabetes mellitus (GDM):
4.1. BMI ≥25 kg/m² (for Indian women, BMI ≥23 kg/m²
4.2. First-degree relative with diabetes
4.3. Previous pregnancy with GDM
4.4. Previous pregnancy with a large baby (≥3.5 kg)
4.5. Previous pregnancy with pre-eclampsia/eclampsia
4.6. History of polycystic ovary disease (PCOD) or impaired fasting glucose
5. Not currently on any medications (excluding iron or folic acid supplements)

Participant type

Other

Age group

Adult

Gender

Female

Target number of participants

1,856 pregnant women (928 from each site)

Participant exclusion criteria

Current inclusion criteria as of 07/05/2020:

1. GDM diagnosed prior to screening visit based on IADPSG criteria or documented
raised HbA1C, i.e., either fasting glucose ≥ 5.1 mmol/L or 1h glucose ≥ 10.0 mmol/L or 2h glucose ≥ 8.5 mmol/L, or a documented HbA1c of ≥ 6.5% at first booking
2. History of pre-gestational diabetes
3. Multiple gestations in the current pregnancy
4. History of severe hyperemesis in the first trimester
5. Uncontrolled pre-gestational or gestational hypertension (BP > 150/100 mmHg) on treatment
6. History of recurrent (≥ 2) first-trimester spontaneous abortions or stillbirths
7. Previous child born with congenital anomalies
8. History of significant ante- or post-partum haemorrhage in the previous pregnancy
9. Pregnancy following in-vitro fertilization or any assisted reproductive technology
10. Previous or current psychiatric illness on medication, epileptic seizures or on antiepileptic medication
11. Women meeting absolute contraindications for physical activity during pregnancy as recommended by the ACOG
11.1. Heart disease
11.2. Restrictive lung disease
11.3. incompetent cervix/cerclage
11.4. Pregnancies at risk for premature labour
11.5. gestational hypertension (BP > 150/100 mmHg)
11.6. Severe anaemia

_____

Previous exclusion criteria:

1. Diagnosis of pre-gestational diabetes, previous GDM based on The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria, or raised blood glucose at blooding - any of the following at first booking:
1.1. Fasting glucose ≥5.1 mmol/L
1.2. 1 hour glucose ≥10.0 mmol/L
1.3. 2 hour glucose ≥8.5 mmol/L
1.4. Documented HbA1c of ≥6.5%
2. Multiple gestation
3. History of severe hyperemesis in first trimester
4. History of hypertension (pre-gestational or gestational)
5. History or recurrent (more than two) first trimester abortions
6. History of ante- or post-partum haemorrhage in the previous pregnancy
7. Previous child born with congenital anomalies
8. Previous stillbirth or miscarriage
9. Pregnancy following in-vitro fertilisation or any assisted reproductive technology
10. Unwilling to adhere to the study protocol
11. History of or current psychiatric illness
12. History of or current neurological condition (i.e. epilepsy)
13. Meeting absolute contraindications for physical activity during preganncy as recommend by the American College of Obstetricians and Gynecologists (ACOG), including:
13.1. Heart disease
13.2. Restrictive lung disease
13.3. Incompetent cervix/cerclage
13.4. At risk for premature labour
13.5. Gestational hypertension
13.6. Severe anaemia

Recruitment start date

01/02/2019

Recruitment end date

31/03/2021

Locations

Countries of recruitment

Gambia, India

Trial participating centre

Christian Medical College
Ida Scudder Road
Vellore
632001
India

Trial participating centre

MRC Unit The Gambia at London School of Hygiene & Tropical Medicine
Atlantic Blvd, Fajara P. O. Box 273
Fajara
273
Gambia

Sponsor information

Organisation

University of Oxford

Sponsor details

Research Services
University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
+44 (0)1865 (2)82106
oxtrec@admin.ox.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Funder name

Department of Biotechnology , Ministry of Science and Technology

Alternative name(s)

DBT

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

India

Funder name

Global Challenges Research Fund, Oxford

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The research findings will be disseminated in national and international platforms and through our network and collaborations. We anticipate publications in high impact international journals and presentation in relevant scientific meetings to inform researchers, clinicians and policy makers. The findings of general linterest will be publicised with the help of the Public Relations Office at the University of Oxford, which is well recognised for being an active communicant of research findings to the public through media. This includes an extensive open website and a full range of events organized during the National Science Week. Furthermore, the School of Medicine runs a very successful engagement programme, in which are its Science in Health, Public Lecture series and Science in Health LIVE event.

IPD sharing statement:
Fully anonymized data will be available on written request from Dr. Senthil Vasan (senthil.vasan@ocdem.ox.ac.uk) after the completion of the study and publication of the primary research findings. All data meant for sharing will be anonymised/de-identified by removing all individual-level participant data and will be archived on the servers of the Archives department of Medical Research Council (MRC) at The Gambia indefinitely. Personally identifiable data will not be shared outside the research team. Data sharing will be in agreement with the MRC, The Gambia as outlined and governed by the Data Sharing Policies and MRC Policy and Guidance on Sharing of Research Data from Population & Patient Studies. The regulations will also adhere to the University of Oxford data policy guidelines. Informed consent for sharing research data with interested collaborators will be obtained from all participants.

Intention to publish date

26/12/2021

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/06/2020: The scientific title has been changed from "PRIMORDIAL: Pregnancy-Related Interventions in MOthers Relating to DIAbetes In Asian India and Low-income countries" to "Pregnancy-Related Interventions in Mothers at Risk for gestational Diabetes in Asian India and Low and middle income countries (PRIMORDIAL Study)". 18/06/2020: Internal review. 17/06/2020: ORCID ID added, interventions and plain English summary updated. The trial was temporarily suspended from 23/03/2020 to 30/05/2020 due to public health regulations. The study has restarted from 01/06/2020 in India. In The Gambia, the study still remains suspended. 16/06/2020: The target number of participants was changed from 1,875 pregnant women to 1,856 pregnant women (928 from each site). 07/05/2020: The following changes were made to the trial record: 1. Due to current public health guidance, recruitment for this study has been paused. 2. The study design was changed from "Interventional 2x2 multi-factorial randomised controlled trial" to "Interventional 2x2 factorial randomized controlled trial". 3. The interventions were changed. 4. The primary outcome measure was changed. 5. The secondary outcome measures were changed. 6. The inclusion criteria were changed. 7. The exclusion criteria were changed. 8. The plain English summary was changed. 11/01/2019: Internal review.